In my last post, I provided an article that laid out the difficulty in getting a cancer vaccine approved by the FDA. The problem is that the law seems to require that the mfg. facility gain approval. Only very strong efficacy results will get the FDA to provide expedited results for Mylovenge from Phase II results.
Well, the good news is that so far they are strong.
Source: SG COWEN SECURITIES CORPORATION, Jul 24, 2000.
Author: TANNER, J.W.
July 24, 2000
- Heading Down The Home Stretch In Phase III Testing
Provenge is Dendreon's prostate cancer vaccine. The antigen is prostatic acid phosphatase (PAP), a protein generally recognized as a marker of prostate cancer. Provenge is the focus of two Phase III trials in which enrollment is ongoing. It is anticipated that approximately 240 patients with metastatic, advanced hormone refractory prostate cancer (HRPC) will be vaccinated at weeks 0, 2 and 4. Endpoints will be disease progression as measured using imaging technologies every eight weeks and the onset of disease-related pain. Blood level of prostate specific antigen (PSA) will also be measured but is not an FDA-accepted endpoint of efficacy. The Provenge arm of the study will have twice the number of patients as the placebo arm. Patient accrual in the studies should be completed over the next 12 months and it is anticipated that a BLA could be filed in the Q1/Q2:2002 time frame. With expedited review, approval and launch could occur in Q3:2002. We project a late Q3 launch.
- Early Trial Data Second To None
Data from Phase I and Phase II clinical trials suggest that Provenge is safe and effective in advanced prostate cancer patients resistant to hormone therapy. In trials conducted at the University of California, San Francisco (UCSF), 53% of HRPC patients vaccinated with Provenge had stable disease at 28 weeks and 26% were stable for more than one year. These results compare favorably with historical disease progression data that indicate 50% of HRPC
patients experience disease progression in 12 weeks. Side effects were minimal (low-grade fever and minor muscle aches), and occurred in less than 2% of patients. A dose-ranging study was also conducted in collaboration with the Mayo Clinic in which 29 advanced prostate cancer patients were treated in sequential Phase I and Phase II clinical trials. The strategy was to test the effectiveness of two doses of Provenge followed by injections of the prostate antigen alone. Six patients receiving Provenge exhibited a decrease in PSA level (one patient had widespread metastases in the lymph nodes).
A collaborative Phase I trial with Asian development partner Kirin Brewery and the National Cancer Center Hospital in Tokyo examined Provenge at different doses for treating HRPC. Consistent with other studies, Provenge was safe with only minimal side effects (low-grade fevers). One of the first four patients to complete treatment experienced a partial remission.
To test Provenge's effectiveness in treating earlier stage patients with smaller tumors, in 1999, Dendreon began a Phase II clinical trial at UCSF. The trial is comprised of relapsed prostate cancer patients who had not received hormone therapy and is designed to assess the effectiveness of Provenge for treatment of newly relapsed prostate cancer. A second trial will be designed to treat men with newly diagnosed prostate cancer. After undergoing surgery to remove the tumor in the prostate, patients will then receive Provenge. Dendreon scientists believe that this process could eliminate residual disease and metastases and thereby prevent recurrence. The company also plans to use these trials as the basis for future Phase III studies intended to expand Provenge labeling.
- Prostate Cancer Market Is Large And Under-served
Affecting approximately 185,000 men per year, prostate cancer is the most prevalent form of cancer in the United States. More than 1MM men are diagnosed with the disease. The five-year survival rate for patients with advanced prostate cancer is only 30%. Treatment for early-stage cancer patients focuses on surgery or radiation therapy. Still, approximately 70% of patients develop metastases. Although hormone therapy (the standard treatment for metastatic prostate cancer) produces temporary tumor control or regression in approximately 80-85% of patients, no treatment improves long-term survival of patients with metastatic prostate cancer. Hormone therapy is problematic in that significant side effects often emerge. With treatment, the cancer can still develop into a condition known as hormone refractory prostate cancer (HRPC). Approximately one half of the patients die within 12-18 months of the onset of HRPC. Treatments for HRPC (chemotherapy and radiopharmaceuticals) alleviate some symptoms, but cause severe side effects and fail to prolong survival.
- Greatest Hurdle Likely To Be Efficacy, Not Competition
Given the shortcomings of current therapies, we believe a scenario in which Provenge is efficacious but fails to gain market share is probably remote. The side effects profile for Provenge is unmatched by existing therapeutics. If the efficacy is supportive of FDA approval, we believe the drug would be adopted as a part of the armamentarium with which to treat advanced prostate cancer. With the provision of efficacy data in treating prostate cancer at earlier stages, the commercial potential could expand. Because most patients eventually fail hormone therapy, it may be that Provenge is not relegated to second-line therapy but, instead, becomes an important primary treatment alternative.
* Mylovenge-Running A Close Second
- Patient-Specific Antigen Is Target
Mylovenge is in Phase II clinical trials for treating certain B-cell malignancies, including multiple myeloma and amyloidosis. These diseases are characterized by abnormal production of immunoglobulins (Ig; antibodies) by
cancerous bone marrow plasma cells. As with therapies for prostate cancer, current treatments are not curative and may cause severe side effects. In contrast with Provenge and other therapeutic vaccines being developed by Dendreon, the antigen for Mylovenge, M protein, is patient-specific. The protein is purified from the patient's blood for use in the vaccine.
- Phase II Data Tantalizingly Good
Dendreon is conducting a Phase II clinical trial of Mylovenge in collaboration with the Mayo Clinic in patients with residual myeloma after high-dose chemotherapy and stem cell transplantation. Of the 13 patients enrolled in the trial thus far, 6 (46%) have experienced major tumor reductions. Four of these patients had complete disappearance of M protein (a surrogate marker of tumor volume), while the other two had a greater than 75% reduction in the level of
M protein. The tumor had also been eradicated from the marrow in the four patients whose M protein had disappeared from the blood. Of the seven remaining patients, six are stable and one had disease progression that
occurred 40 weeks after starting treatment. These results suggest that Mylovenge is safe, has few side effects, and may be effective for treating multiple myeloma that is resistant to high-dose chemotherapy. Also as part of this trial, five patients with amyloidosis are being treated. Evidence of significant clinical improvement has been observed to damaged organs in three of the five patients. In response to these results, additional amyloidosis patients are being enrolled in this trial.
In addition to testing Mylovenge in patients who are resistant to high-dose chemotherapy, Dendreon is also conducting a 34-patient, Phase II multi-center clinical trial for the treatment of patients with high tumor volume resistant to standard chemotherapy. One half of these patients have shown signs of clinical benefit, with decreased M protein in five patients and stable M protein for at least 24 weeks in 12 patients. Standard treatment typically
results in disease progression within eight to 12 weeks of initiating treatment in 50% of patients.
Patients experienced few side effects. Given the product's success in this trial, Dendreon has extended its scope to establish efficacy in patients with low tumor volume after stem cell transplantation. Further, the company hopes
to initiate a trial for multiple myeloma patients with low tumor volume after standard dose chemotherapy.
Assuming positive results from these studies, Dendreon plans to initiate Phase III trials in 2001. It is possible, however, that data from the ongoing studies could form the basis for a BLA submission to the FDA. If so, we would
project the drug could reach the market sooner than expected. We currently model Mylovenge being launched in the mid-2003 time frame. |
